Endocrinology 5 - Hyperthyroid disorders Flashcards
List the classes of drugs used in treatment of hyperthyroidism
- Thionamides (thiourylenes; anti-thyroid drugs eg. peopylthiouracil [PTU] and carbimazole)
- Potassium iodide
- Radioiodine
- B-blockers
- First 3 reduce thyroid hormone synthesis, while beta-blockers don’t affect synthesis but help to manage the symptoms
List the uses of thionamides
- Daily treatment of hyperthyroid conditions (Graves/ toxic thyroid nodule)
- Treatment prior to surgery
- Reduction of symptoms while waiting for radioactive iodine to act
Briefly summarise thyroid hormone synthesis
- Uptake of iodide by active transport
- Iodination
- Coupling reaction (storage in colloid) makes T3/T4
- Endocytosis
Describe the mechanism of action of thionamides
- Inhibition of thyroid peroxidase and hence T3/4 synthesis and secretion
- May suppress antibody production in Graves disease
- Reduces conversion of T4 to T3 in peripheral tissues
List the unwanted actions of thionamides
- Agranulocytosis (reduction in neurophils) - rare and reversible
- Rashes
Describe the pharmacokinetics of thionamides
- Orally active
- Carbimazole is a pro-drug which first has to be converted to metimazole
- Cross placenta, secreted in breastmilk (carbimazole more than PTU)
- Metabolised in the liver and excreted in urine
What is the follow up procedure in patients on thionamides?
- Usually aim to stop anti-thyroid drug treatment after 18 months
- Review periodically including thyroid function tests for remission/relapse
How are beta blockers used in thyrotoxicosis treatment?
- Several weeks for ATDs to have clinical effects (reduced tremor, slower heart rate and less anxiety)
- Non-selective beta blockers like propanolol achieve these effects in the meantime
When are (potassium) iodides used in thyrotoxicosis treatment?
- Preparation of hyperthyroid patients for surgery
- Severe thyrotoxic crisis (thyroid storm) - they allow you to act quickly
List the unwanted actions of potassium iodide?
Allergic reactions (rashes, fever and angiooedema)
Describe the parmacokinetics of potassium iodide
- Given orally (lugols solution or aqueous iodine)
- Maximum effects after 10 days continuous administration
List the uses of radioiodine and its mechanism
- Treats hyperthyroidism (graves/toxic nodular disease) and thyroid cancers.
- Before pregnancy this would work so the patient wouldn’t need to take any anti-thyroid drugs
- Accumulates in colloid and emits beta particles, destroying follicular cells
Describe the pharmacokinetics of radioiodine
- Discontinue anti-thyroid drugs 7-10 days prior to radioiodine treatment
- Administered as a single oral dose
- Radioactive half life of 8 days
- Radioactivity negligible after 2 months
List the cautions of radioiodine treatment
- Avoid close contact with small children for several weeks after receiving radioiodine
- Contra-indicated in pregnancy (wait 6 months) and breast feeding
What causes hyperthyroidism?
- Graves disease (autoimmune)
- Nodular goitre (plummers disease)
List the characteristics of graves disease?
- Antibodies stimulate TSH receptor
- Cause a smooth goitre and hyperthyroidism
List the features of hyperthyroidism
- Diarrhoea
- Nervousness
- Tachycardia
- Palpatations
- Loss of weight
- Very hungry
- Tremour
- Muscle weakness
- Localised pretibial myxoedema (no pits form when pressed)
- Graves opthalmopathy and exopthalmos (big staring eyes)
- Lid lag
- Breathlessness
- Causes the eyes to bulge and shins to swell (three different antibodies cause each)
What is plummers disease caused by?
- A benign tumour of the thyroid fland
- Not autoimmune, no pretibial myxoedema, no smoothly enlarged goitre - it is nodular (one part of the thyroid gland grows - hot nodule).
- As one part of the thyroid gland is producing lots of thyroxine, the rest of the thyroid gland begins to shrink
List the effects of thyroxine on the SNS
- Sensitises beta-adrenoreceptors to ambient levels of adrenaline and noradrenaline
- There is apparent sympathetic stimulation
- This results in tachycardia, palpitations, tremour in hands and lid lag
How is hyperthyroidism identified (not including blood test)?
- Test for lid lag (lids close just after eyes go down, so you can see whites of their eyes at the top)
- Ask the patient to swallow water and feel the thyroif gland for goitre
What is a thyroid storm?
- Patient has very very high thyroxine levels
- 50% mortality when untreated
List the features of thyroid storm.
- Cardiac failure
- Delirium/ frank psychosis
- Hepatocellular dysfunction (jaundice)
- Hyperpyrexia (>41 degrees)
- Arrythmia/tachycardia
How can thyroid storm be treated?
- Surgery (thyroidectomy)
- Radioiodine
- Drugs
How quickly do thionamides work?
- Biochemically it takes hours
- Clinical effect takes weeks, so the symptoms are not improving
